Brexucabtagene Autoleucel with Dasatinib for Acute Lymphoblastic Leukemia
Phase 1b Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia
This study is testing if combining a new CAR T-cell treatment with a medication called dasatinib can help adults with relapsed or hard-to-treat B-cell acute lymphoblastic leukemia feel better.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Stanford University Academic / other |
| Drugs / interventions | blinatumomab, dasatinib, chemotherapy |
| Locations | 1 site (Palo Alto, California) |
| Trial ID | NCT05993949 on ClinicalTrials.gov |
What this trial studies
This study evaluates the feasibility of administering oral dasatinib in conjunction with brexucabtagene autoleucel (Tecartus) in adults suffering from relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Participants will receive dasatinib in pulses for three consecutive days each week during the first month after their CAR T-cell infusion. The goal is to determine the safety and effectiveness of this combination therapy in improving patient outcomes.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory B-precursor ALL.
Not a fit: Patients with non-B-precursor ALL or those who are not relapsed or refractory may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could enhance treatment efficacy for patients with difficult-to-treat forms of acute lymphoblastic leukemia.
How similar studies have performed: Other studies have shown promise with CAR T-cell therapies, but the specific combination of brexucabtagene autoleucel and dasatinib is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* Relapsed or refractory B-precursor ALL defined as one of the following:
* Primary refractory disease (\>=5% blasts or persistent extramedullary disease following induction therapy)
* First or later relapse of marrow or extramedullary disease
* Persistence of MRD defined as detectable ALL by flow cytometry, PCR, or next-generation sequencing
* Relapsed or refractory disease after allogeneic transplant provided individual is at least 100 days from transplant at time of enrollment
* Patients with isolated, asymptomatic CNS relapse will be eligible
* Age \>=18 years
* Eastern cooperative oncology group (ECOG) performance status of 0-2
* Adequate renal, hepatic, pulmonary and cardiac function defined as:
* Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min
* Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dl, except in individuals with Gilbert's syndrome.
* Cardiac ejection fraction ≥ 50%, no evidence of clinically significant pericardial effusion, and no clinically significant arrhythmias
* Baseline oxygen saturation \> 92% on room air
* QTc ≤ 500ms
* In individuals previously treated with blinatumomab, CD19 tumor expression in bone marrow or peripheral blood by flow cytometry or extramedullary site by IHC or flow cytometry
* Negative serum or urine beta-HCG test in females of childbearing potential within 3 weeks of enrollment
* Subjects of childbearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study Page 10 of 83 Version 1.0 dated 27-April-2023 and for six (6) months after receiving the preparative conditioning regimen.
* Must be able to give informed consent. Legal authorized representative (LAR) is permitted if subject is cognitively able to provide verbal assent.
Exclusion Criteria:
* History of dasatinib intolerance
* Known sensitivity or allergy to aminoglycosides or any agents/reagents used in this study
* Blast count \> 75% in the bone marrow.
* History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 2 years
* Presence of CNS-3 disease with neurological changes
* History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage with clinical signs or symptoms
* History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond or any known bone marrow failure syndrome
* History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
* Primary immunodeficiency
* Known infection with HIV, hepatitis B (HBsAg positive) or untreated hepatitis C virus
* Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
* Salvage chemotherapy including TKIs for Ph+ ALL within 1 week prior to enrollment
* Pregnant or breast feeding
* Patients with known autoimmune disease requiring the use of systemic immunosuppressive therapy within the last year
* Corticosteroid therapy within 7 days prior to enrollment
* Acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
* Live vaccine ≤ 4 weeks prior to enrollment
* Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment
Where this trial is running
Palo Alto, California
- Stanford University — Palo Alto, California, United States (Recruiting)
Study contacts
- Principal investigator: Lori Muffly, M.D. — Stanford University
- Study coordinator: Alyssa M Kanega
- Email: akanegai@stanford.edu
- Phone: 650-736-1596
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.